综合的单细胞多基因分析揭示了与衰老相关的造血图景和骨髓衰老中的调节网络
Guoyang Zhang1,2,3, Weixuan Lin4,5,6, Linghuan Guo4,5,7
1Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China. GY_Zhang2023@163.com.
Biogerontology
|November 24, 2025
概括
老化骨髓显示了一个新的细胞群激活衰老和炎症. 一个CAPN1-MAP2K1-JUND模块预测衰老,提供有关骨髓衰老机制和治疗点的见解.
科学领域:
- 老年学是一门学科.
- 血液学 血液学 血液学
- 分子生物学分子生物学
背景情况:
- 骨髓衰老导致功能衰退,但其细胞和分子基础尚未完全理解.
- 传统方法在描述与年龄相关的骨髓变化的复杂性方面存在局限性.
研究的目的:
- 在细胞和分子层面上描述骨髓与年龄相关的变化.
- 为了确定关键的分子驱动因素和信号通路参与骨髓衰老.
主要方法:
- 包括单细胞RNA测序 (scRNA-seq),蛋白质组学和伪批量转录组学在内的综合多组学分析.
- 权重基因共同表达网络分析 (WGCNA) 用于转录因子 (TF) 网络建模和CellChat用于细胞间通信分析.
- 使用差异表达式分析,考克斯回归和接收器运行特征 (ROC) 曲线分析对独立队列进行统计验证.
主要成果:
- 在老年骨髓中发现了一种新的造血子群,其特征是细胞衰老途径的激活和通过NMU信号与CD8+T细胞增强的炎症交叉声.
- 伪散装和蛋白质组分析强调了CAPN1,MAP2K1和JUND作为分子模块的关键组成部分.
- CAPN1-MAP2K1-JUND模块在两个独立的散装RNA队列中显示出强大的衰老预测价值,具有高的曲线下面面积 (AUC) 值.
结论:
- 这项研究确定了一个关键的分子模块,将单细胞动态与骨髓中的组织水平衰老联系起来.
- 这些发现为骨髓衰老的机制提供了新的见解.
- 已识别的模块和途径代表了与年龄相关的骨髓功能障碍的潜在治疗点.
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